Time resolved optical spectroscopy in photodissociation experiments and molecular dynamics simulations are being used to investigate protein folding and structure function relations in heme proteins. Fast events in the folding of cytochrome c are being studied by optically triggering the folding reaction with nanosecond laser pulses. Before folding begins we observe transient binding of both non-native and native ligands from the unfolded polypeptide on a microsecond time scale. This optical trigger should provide a powerful method for studying chain collapse and secondary structure formation in cytochrome c without any limitations in time- resolution. Kinetic and theoretical studies on ligand binding in myoglobin have yielded new important information on the mechanism, including the finding that the viscosity dependence of the protein conformational relaxation rate can be explained using a modification of Kramers theory which includes the contributions of both protein and solvent to the friction, the demonstration that all of the major features of myoglobin kinetics at ambient temperatures can be explained with a "minimal" model that includes a fast and slow rebinding conformation and two geminate states for each conformation, and the finding that the rate of escape of the photodissociated ligand from the energy well adjacent to the heme calculated from molecular dynamics simulations is in good agreement with the value calculated from experimental data, suggesting that multiple geminate states should be an integral part of a kinetic model. We have begun to investigate the role of increased intracellular polymerization as a cause of more severe clinical severity in patients with homozygous sickle cell disease by using our laser photolysis - light scattering technique on individual cells to measure the distribution of intracellular delay times in patients with varying degrees of clinical severity and comparing these distributions before and after the beginning of hydroxyurea therapy.